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Fragment screening of inhibitors for MIF tautomerase reveals a cryptic surface binding site
Fragment screening by in silico docking followed by X-ray crystallography demonstrates the formation of a previously unreported surface binding site in MIF that is hydrophobic and surrounded by aromatic side-chain residues. In the course of a fragment screening campaign by in silico docking followed...
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Published in: | Bioorganic & medicinal chemistry letters 2010-03, Vol.20 (6), p.1821-1824 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Fragment screening by in silico docking followed by X-ray crystallography demonstrates the formation of a previously unreported surface binding site in MIF that is hydrophobic and surrounded by aromatic side-chain residues.
In the course of a fragment screening campaign by in silico docking followed by X-ray crystallography, a novel binding site for migration inhibitory factor (MIF) inhibitors was demonstrated. The site is formed by rotation of the side-chain of Tyr-36 to reveal a surface binding site in MIF that is hydrophobic and surrounded by aromatic side-chain residues. The crystal structures of two small inhibitors that bind to this site and of a quinolinone inhibitor, that spans the canonical deep pocket near Pro-1 and the new surface binding site, have been solved. These results suggest new opportunities for structure-based design of MIF inhibitors. |
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ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2010.02.009 |